Therapeutic hypothermia: Difference between revisions

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==Background==
==Background==
*Determination of Neurologic Prognosis is unreliable before at least 72 hours after ROSC. Do not neuroprognosticate until 72 hours post rewarming.
*Determination of Neurologic Prognosis is unreliable before at least 72 hours after ROSC
*Greatest benefit in out-of-hospital V-fib, though evidence suggests hypothermia helps in other dysrhythmias<ref>Nolan, et al. Therapeutic Hypothermia After Cardiac Arrest. Circulation. 2003; 108: 118-121.</ref>
**Do not neuroprognosticate until 72 hours post rewarming.
*Greatest benefit in out-of-hospital V-fib, though may help in other dysrhythmias<ref>Nolan, et al. Therapeutic [[Hypothermia]]After Cardiac Arrest. Circulation. 2003; 108: 118-121.</ref>
*Two most likely mechanisms of action:
*Two most likely mechanisms of action:
**Reduces cerebral metabolism by 6-8% per degree C
**Reduces cerebral metabolism by 6-8% per degree C
**Reduces oxygen free radical production and lipid peroxidation
**Reduces oxygen free radical production and lipid peroxidation
*Cooling to 32-34ºC was found in initial studies, current studies suggest 36ºC to have same benefits<ref>Nielsen N, et al. Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest. N Engl J Med. 2013; 369:2197-2206. DOI: 10.1056/NEJMoa1310519</ref>
*Cooling to 32-34ºC in initial studies, current studies suggest 36ºC equally beneficial<ref>Nielsen N, et al. Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest. N Engl J Med. 2013; 369:2197-2206. DOI: 10.1056/NEJMoa1310519</ref>
*Therapeutic hypothermia does not appear to provide a survival or improved neurological benefit in the pediatric population<ref>Mosler FW, et al. Therapeutic hypothermia after out-of-hospital cardiac arrest in children. N Eng J Med. 2015; 372:1898-1908.</ref>
*Treatment should be initiated immediately after ROSC
*Therapeutic hypothermia should be initiated immediately after ROSC, and patient may be cooled concurrently with cardiac catheterization
**Patient may be cooled concurrently with cardiac catheterization
*Cooling should occur prior to CT scan if there is need for intracranial pathology workup  
*Cooling should occur prior to CT scan if there is need for intracranial pathology workup  
*AHA recommends 12-24 hrs of cooling
*AHA recommends 12-24 hrs of cooling
*NNT of ~6
*NNT of ~6
*Pediatrics<ref>Moler FW et al. Therapeutic Hypothermia after In-Hospital Cardiac Arrest in Children. N Engl J Med 2017; 376:318-329January 26, 2017.</ref><ref>Moler FW et al. Therapeutic Hypothermia after Out-of-Hospital Cardiac Arrest in Children. N Engl J Med 2015; 372:1898-1908May 14, 2015.</ref>
**Two large RTCs for TH, one in out-of-hospital and another in in-hospital arrests
**Therapeutic hypothermia does not appear to provide a survival or improved neurological benefit<ref>Mosler FW, et al. Therapeutic hypothermia after out-of-hospital cardiac arrest in children. N Eng J Med. 2015; 372:1898-1908.</ref>
***In both studies, '''no difference''' in survival, function at 12 months post-arrest, blood product use, infection rates


==Indications==
==Indications==
*V-fib arrest
*[[Vfib]] arrest
*Other pulseless dysrhythmias (relative)
*Other pulseless [[dysrhythmias]] (relative)


==Contraindications/Exclusions==
==Contraindications/Exclusions==
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*Glasgow Motor score  >5
*Glasgow Motor score  >5
*Minimal pre-morbid cognitive status
*Minimal pre-morbid cognitive status
*Unable to maintain SBP > 90 mmHg, with or without pressors, after CPR
*Unable to maintain [[shock|SBP > 90 mmHg]], with or without pressors, after CPR
*Other reason for coma
*Other reason for coma
**Intracranial pathology (i.e. intracranial hemorrhage, ischemic stroke)
**Intracranial pathology (i.e. [[intracranial hemorrhage]], ischemic [[stroke]])
**Subarachnoid hemorrhage
**[[Subarachnoid hemorrhage]]
**Sedation
**[[Sedation]]
**Drug overdose
**[[Drug overdose]]
**Status epilepticus
**[[Status epilepticus]]
*Sepsis as etiology for arrest
*[[Sepsis]] as etiology for arrest
*DNR/DNI status, terminal illness
*DNR/DNI status, terminal illness
*Uncontrollable bleeding or known bleeding diathesis with active bleeding
*Uncontrollable bleeding or known [[coagulopathy|bleeding diathesis]] with active bleeding
*Significant trauma (especially intra-abdominal)
*Significant [[trauma]] (especially intra-abdominal)
*Pregnancy
*[[Pregnancy]]
*Therapeutic hypothermia may be safe for postpartum cardiac arrest<ref>Song et al. Safely completed therapeutic hypothermia in postpartum cardiac arrest survivors. Am Jour Emer Med. June 2015. Volume 33, Issue 6, Pages 861.e5–861.e6.</ref>
*Therapeutic hypothermia may be safe for postpartum cardiac arrest<ref>Song et al. Safely completed therapeutic hypothermia in postpartum cardiac arrest survivors. Am Jour Emer Med. June 2015. Volume 33, Issue 6, Pages 861.e5–861.e6.</ref>


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**Supplement with ice packs to groin, chest, axillae, neck until 34ºC reached
**Supplement with ice packs to groin, chest, axillae, neck until 34ºC reached
*Prevention of shivering and paralysis
*Prevention of shivering and paralysis
**Use [[benzodiazepines]]
**Paralytics only if needed, and ensure patient fully sedated


==Maintainance==
==Maintenance==
===Sedation===
===[[Sedation]]===
*Fentanyl Injection 50 mcg IV every hour as needed for pain
*[[Fentanyl]] bolus 50 mcg IV every hour as needed for pain
*Fentanyl IV infusion NSS
*Fentanyl IV infusion NSS
*Propofol IV infusion  
*[[Propofol]] IV infusion  
*Lorazepam IV infusion
*[[Lorazepam]] IV infusion
*Lorazepam Injection 1 mg IV every 2 hours as needed for agitation
*Lorazepam bolus 1mg IV every 2 hours as needed for agitation
===Shivering===
===Shivering===
*Prevention of shivering is important to avoid warming and needless oxygen consumption
*Prevention of shivering is important to avoid warming and needless oxygen consumption
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**Decrease plateau pressures
**Decrease plateau pressures
**Hypoxemia is present
**Hypoxemia is present
*Consider meperidine q2hrs<ref>Choi HA, Ko SB, Presciutti M, et al. Prevention of Shivering During Therapeutic Temperature Modulation: The Columbia Anti-Shivering Protocol. Neurocrit Care. 2011; 14(3):389-394.</ref><ref>Fox Chase Cancer Center. Therapeutic Hypothermia Protocol. University of Pennsylvania. https://www.med.upenn.edu/resuscitation/docs/protocols/FoxChaseCancerCenterTherapeuticHypothermiaOrderSetafterCardiacArrest-latestrevision8-4-11.doc</ref>:
*Consider [[meperidine]] q2hrs<ref>Choi HA, Ko SB, Presciutti M, et al. Prevention of Shivering During Therapeutic Temperature Modulation: The Columbia Anti-Shivering Protocol. Neurocrit Care. 2011; 14(3):389-394.</ref><ref>Fox Chase Cancer Center. Therapeutic [[Hypothermia]]Protocol. University of Pennsylvania. https://www.med.upenn.edu/resuscitation/docs/protocols/FoxChaseCancerCenterTherapeuticHypothermiaOrderSetafterCardiacArrest-latestrevision8-4-11.doc</ref>:
**50 mg for normal renal function
**50mg for normal renal function
**25 mg if CrCl < 30 ml/min
**25mg if CrCl < 30ml/min
*Pancuronium IV infusion  
*[[Pancuronium]] IV infusion  
**Initiate before initiating cooling. Dosing recommendations: 0.1 mg/kg loading dose followed by a continuous infusion of 0.33-2 mcg/kg/minute
**Initiate before initiating cooling. Dosing recommendations: 0.1mg/kg loading dose followed by a continuous infusion of 0.33-2 mcg/kg/minute
**Do not use in patients with renal and/or hepatic insufficiency
**Do not use in patients with renal and/or hepatic insufficiency
*Cisatricurium for renal/hepatic impairment
*Cisatracurium for renal/hepatic impairment
**0.2 mg/kg IV bolus
**0.2mg/kg IV bolus
**Followed by infusion at 1 mcg/kg/min, max of 3 mcg/kg/min
**Followed by infusion at 1 mcg/kg/min, max of 3 mcg/kg/min
*Columbia University anti-shivering protocol
[[File:columbia shivering protocol.PNG|thumbnail]]


==Rewarming==
==Rewarming==
*If severe dysrhythmia/BP instability/bleeding develops, rewarm pt
*If severe dysrhythmia/BP instability/bleeding develops, rewarm
*D/c K infusions (extracellular K increases)
*Discontinue K infusions (extracellular K increases)
*Keep paralytic and sedative until rewarmed
*Keep paralytic and sedative until rewarmed
*Slow rewarm at 0.5°C to target of 36°C
*Slow rewarm at 0.5°C to target of 36°C


==General Management==
==General Management==
===Other Concerns==
===Other Concerns===
*Head of bed at 30 degrees
*Head of bed at 30 degrees
*Goal MAP 80 - 100 mmhg
*Goal MAP 80 - 100 mmhg
**Titrate with norepinephrine (start 2-4 mcg/min) if EF > 50%
**Titrate with [[norepinephrine]] (start 2-4 mcg/min) if EF > 50%
**Titrate with dobutamine (start 2.5-20 mcg/kg/min) if EF < 50%
**Titrate with [[dobutamine]] (start 2.5-20 mcg/kg/min) if EF < 50%
**IV NTG starting at 10 mcg/min if HTN
**IV [[nitroglycerin]] starting at 10 mcg/min if hypertensive
*Check skin q2-6 hrs for cold injury
*Check skin q2-6 hrs for cold injury
*Maintain tight BG control, 110-150 mg/dL
*Maintain normoglycemia
**Do not treat [[hyperglycemia]] aggressively, as enzymatic functions are decreased at low temperatures, and rebound hypoglycaemia possible with rewarming
*Replete K, Mg, Phos, Ca (hypothermia induced diuresis is expected)
*Replete K, Mg, Phos, Ca (hypothermia induced diuresis is expected)
*Common unconcerning ECG findings during cooling - Osborne wave, HR < 40 bpm
*Common unconcerning ECG findings during cooling - Osborne wave, HR < 40 bpm
*Consider continuous EEG within 6 hrs, no later than 12 hrs after onset of cooling
*Consider continuous EEG within 6 hrs, no later than 12 hrs after onset of cooling
*Stress dose steroids for adrenal insufficiency
*Stress dose [[steroids]] for adrenal insufficiency
*?[[Seizure]] prophylaxis


===Labs===
===Labs===
*ABG q6 hrs for duration of hypothermia
*ABG q6 hrs for duration of hypothermia
*CBC, Coags, BMP, Mg, Phos q6 hrs for duration of hypothermia (expect decreased K, Ca, Mg, Phos during, and rebound at rewarming)
*CBC, Coags, BMP, Mg, Phos q6 hrs for duration of hypothermia
*Troponins, CK-MB q6 hrs x2 days
**Expect decreased K, Ca, Mg, Phos during, and rebound at rewarming
**Hyperglycemia as metabolism slows at low temperature and body develops insulin resistance
*[[Troponin]]s, CK-MB q6 hrs x2 days
*Lipase, LFTs (if abnormal, no need to intervene unless persistent after rewarming)
*Lipase, LFTs (if abnormal, no need to intervene unless persistent after rewarming)
*Other - Cortisol, UA, Pan-cultures, tox screen
*Other - Cortisol, UA, Pan-cultures, tox screen


===ABG Interpretation===
===[[ABG]] Interpretation===
*Rewarm ABG to 37 ℃ for analysis
*Rewarm ABG to 37C for analysis (controversial)
*If not rewarmed, the following are seen for every 1°C below 37°C:
*A warmed ABG from a hypothermic patient will show a  higher PaO2, higher PaCO2, and a lower pH than that actually present in the patient’s blood ''in vivo''
**PO2 overestimated by 5 mmHg
**PaO2 is decreased by 5 mmHg for each degree below 37C
**PCO2 overestimated by 2 mmHg
**PaCO2 is decreased by 2 mmHg for each degree below 37C
**pH underestimated by 0.012
**Change in pH = 0.015 pH units per degree C change in temperature
***If measured pH is 7.360 at 37C, then the pH at 34C is calculated as follows:
****pH = [7.360 + (37-34)(0.015)] = 7.405


===Monitoring===
===Monitoring===
*ECG q8 r/o ACS
*[[ECG]] q8 rule out ACS
*Arterial line
*Arterial line
*Foley with temp probe
*Foley with temperature probe
*CVP, ScvO2
*CVP, ScvO2


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*Consider head CT
*Consider head CT
*Consider CTPE study
*Consider CTPE study
===Other Considerations===
*GI prophylaxis
*Modify prophylactic [[heparin]] or [[LMWH]] dosing as there is hypothermic coagulopathy<ref>Wahby KA et al. Heparin dosing in critically ill patients undergoing therapeutic hypothermia following cardiac arrest. Resuscitation. 2014 Apr;85(4):533-7.</ref>
**No clear best way for monitoring of anticoagulation until further studies
**Consider modified dosing:
***Heparin 40 units IV bolus
***Followed by 7 u/kg/hr during TH with scheduled repeated coags, plus or minus heparin levels


==Disposition==
==Disposition==
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==External Links==
==External Links==
*[http://www.acep.org/Clinical---Practice-Management/Focus-On--Therapeutic-Hypothermia/ Focus On: Therapeutic Hypothermia]
*[http://www.acep.org/Clinical---Practice-Management/Focus-On--Therapeutic-Hypothermia/ Focus On: Therapeutic Hypothermia]
*[http://www.emrap.org/episode/august2013/therapeutic EMRAP:Therapeutic Hypothermia with Amal Mattu, MD FAAEM]
*[http://www.emrap.org/episode/august2013/therapeutic EMRAP:Therapeutic [[Hypothermia]]with Amal Mattu, MD FAAEM]


==See Also==
==See Also==

Latest revision as of 17:12, 26 September 2019

Background

  • Determination of Neurologic Prognosis is unreliable before at least 72 hours after ROSC
    • Do not neuroprognosticate until 72 hours post rewarming.
  • Greatest benefit in out-of-hospital V-fib, though may help in other dysrhythmias[1]
  • Two most likely mechanisms of action:
    • Reduces cerebral metabolism by 6-8% per degree C
    • Reduces oxygen free radical production and lipid peroxidation
  • Cooling to 32-34ºC in initial studies, current studies suggest 36ºC equally beneficial[2]
  • Treatment should be initiated immediately after ROSC
    • Patient may be cooled concurrently with cardiac catheterization
  • Cooling should occur prior to CT scan if there is need for intracranial pathology workup
  • AHA recommends 12-24 hrs of cooling
  • NNT of ~6
  • Pediatrics[3][4]
    • Two large RTCs for TH, one in out-of-hospital and another in in-hospital arrests
    • Therapeutic hypothermia does not appear to provide a survival or improved neurological benefit[5]
      • In both studies, no difference in survival, function at 12 months post-arrest, blood product use, infection rates

Indications

Contraindications/Exclusions

Cooling

  • Cool to 32-34ºC as soon as possible (within 4 hours)
    • Strict maintenance of temperature at 36ºC may have similar benefits
  • Initiate rewarming 24 hrs after target temperature was reached
  • Cooling methods
    • Maintain at 32-34ºC with 2 cooling blankets to sandwich the pt, with sheets covering the blankets to protect skin
    • Alternatively, use heat exchange device (Icy Cath) or 4°C IVF at 30 cc/kg over 30 min
    • Cooling pads on the thighs and abdomen (Arctic Sun)
    • Supplement with ice packs to groin, chest, axillae, neck until 34ºC reached
  • Prevention of shivering and paralysis
    • Use benzodiazepines
    • Paralytics only if needed, and ensure patient fully sedated

Maintenance

Sedation

  • Fentanyl bolus 50 mcg IV every hour as needed for pain
  • Fentanyl IV infusion NSS
  • Propofol IV infusion
  • Lorazepam IV infusion
  • Lorazepam bolus 1mg IV every 2 hours as needed for agitation

Shivering

  • Prevention of shivering is important to avoid warming and needless oxygen consumption
  • May require train of four monitor with goal of 1-2/4 twitches with neuromuscular blockade
  • Lower doses of NMB work against shivering
  • Higher doses of NMB used to paralyze the diaphragm in these scenarios:
    • Need to decrease O2 consumption
    • Decrease plateau pressures
    • Hypoxemia is present
  • Consider meperidine q2hrs[7][8]:
    • 50mg for normal renal function
    • 25mg if CrCl < 30ml/min
  • Pancuronium IV infusion
    • Initiate before initiating cooling. Dosing recommendations: 0.1mg/kg loading dose followed by a continuous infusion of 0.33-2 mcg/kg/minute
    • Do not use in patients with renal and/or hepatic insufficiency
  • Cisatracurium for renal/hepatic impairment
    • 0.2mg/kg IV bolus
    • Followed by infusion at 1 mcg/kg/min, max of 3 mcg/kg/min
  • Columbia University anti-shivering protocol
Columbia shivering protocol.PNG

Rewarming

  • If severe dysrhythmia/BP instability/bleeding develops, rewarm
  • Discontinue K infusions (extracellular K increases)
  • Keep paralytic and sedative until rewarmed
  • Slow rewarm at 0.5°C to target of 36°C

General Management

Other Concerns

  • Head of bed at 30 degrees
  • Goal MAP 80 - 100 mmhg
  • Check skin q2-6 hrs for cold injury
  • Maintain normoglycemia
    • Do not treat hyperglycemia aggressively, as enzymatic functions are decreased at low temperatures, and rebound hypoglycaemia possible with rewarming
  • Replete K, Mg, Phos, Ca (hypothermia induced diuresis is expected)
  • Common unconcerning ECG findings during cooling - Osborne wave, HR < 40 bpm
  • Consider continuous EEG within 6 hrs, no later than 12 hrs after onset of cooling
  • Stress dose steroids for adrenal insufficiency
  • ?Seizure prophylaxis

Labs

  • ABG q6 hrs for duration of hypothermia
  • CBC, Coags, BMP, Mg, Phos q6 hrs for duration of hypothermia
    • Expect decreased K, Ca, Mg, Phos during, and rebound at rewarming
    • Hyperglycemia as metabolism slows at low temperature and body develops insulin resistance
  • Troponins, CK-MB q6 hrs x2 days
  • Lipase, LFTs (if abnormal, no need to intervene unless persistent after rewarming)
  • Other - Cortisol, UA, Pan-cultures, tox screen

ABG Interpretation

  • Rewarm ABG to 37C for analysis (controversial)
  • A warmed ABG from a hypothermic patient will show a higher PaO2, higher PaCO2, and a lower pH than that actually present in the patient’s blood in vivo
    • PaO2 is decreased by 5 mmHg for each degree below 37C
    • PaCO2 is decreased by 2 mmHg for each degree below 37C
    • Change in pH = 0.015 pH units per degree C change in temperature
      • If measured pH is 7.360 at 37C, then the pH at 34C is calculated as follows:
        • pH = [7.360 + (37-34)(0.015)] = 7.405

Monitoring

  • ECG q8 rule out ACS
  • Arterial line
  • Foley with temperature probe
  • CVP, ScvO2

Imaging

  • Consider head CT
  • Consider CTPE study

Other Considerations

  • GI prophylaxis
  • Modify prophylactic heparin or LMWH dosing as there is hypothermic coagulopathy[9]
    • No clear best way for monitoring of anticoagulation until further studies
    • Consider modified dosing:
      • Heparin 40 units IV bolus
      • Followed by 7 u/kg/hr during TH with scheduled repeated coags, plus or minus heparin levels

Disposition

  • ICU admission

External Links

See Also

Hypothermia Cardiac Arrest Links

References

  1. ↑ Nolan, et al. Therapeutic HypothermiaAfter Cardiac Arrest. Circulation. 2003; 108: 118-121.
  2. ↑ Nielsen N, et al. Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest. N Engl J Med. 2013; 369:2197-2206. DOI: 10.1056/NEJMoa1310519
  3. ↑ Moler FW et al. Therapeutic Hypothermia after In-Hospital Cardiac Arrest in Children. N Engl J Med 2017; 376:318-329January 26, 2017.
  4. ↑ Moler FW et al. Therapeutic Hypothermia after Out-of-Hospital Cardiac Arrest in Children. N Engl J Med 2015; 372:1898-1908May 14, 2015.
  5. ↑ Mosler FW, et al. Therapeutic hypothermia after out-of-hospital cardiac arrest in children. N Eng J Med. 2015; 372:1898-1908.
  6. ↑ Song et al. Safely completed therapeutic hypothermia in postpartum cardiac arrest survivors. Am Jour Emer Med. June 2015. Volume 33, Issue 6, Pages 861.e5–861.e6.
  7. ↑ Choi HA, Ko SB, Presciutti M, et al. Prevention of Shivering During Therapeutic Temperature Modulation: The Columbia Anti-Shivering Protocol. Neurocrit Care. 2011; 14(3):389-394.
  8. ↑ Fox Chase Cancer Center. Therapeutic HypothermiaProtocol. University of Pennsylvania. https://www.med.upenn.edu/resuscitation/docs/protocols/FoxChaseCancerCenterTherapeuticHypothermiaOrderSetafterCardiacArrest-latestrevision8-4-11.doc
  9. ↑ Wahby KA et al. Heparin dosing in critically ill patients undergoing therapeutic hypothermia following cardiac arrest. Resuscitation. 2014 Apr;85(4):533-7.
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